The present disclosure relates generally to hydrogel microspheres for use in removing or otherwise reducing the activity of growth factors from blood products. Particularly, vascular endothelial growth factor (VEGF)-sequestering hydrogel microspheres have been prepared to selectively bind VEGF from blood products, thereby regulating VEGF activity for applications wherein VEGF activity may be deleterious for wound healing. In one particular embodiment, the microspheres bind VEGF as part of an intra-operative process such that the growth factor can be removed from the blood products before the products are used in a clinical procedure.
Angiogenesis during wound healing involves a complex interplay of vascular and stromal cells, the extracellular matrix, and platelets that are activated upon wound healing stimuli. Platelet activation initiates growth factor release and subsequent growth factor signaling to cells in the wound healing milieu. For example, activated platelets release vascular endothelial growth factor (VEGF), which signals to vascular endothelial cells (ECs) and initiates angiogenic sprouting during early wound healing. VEGF must be maintained in a limited concentration range to initiate angiogenesis during wound healing and ultimately to form patent new vasculature. Unregulated VEGF expression often results in hemangioma formation in vivo, and high levels of VEGF activity promote aberrant angiogenesis associated with poor musculoskeletal wound healing and disease pathology, including ocular disease.
The native extracellular matrix (ECM) modulates the cell response to VEGF, and synthetic biomaterials designed to mimic the ECM can regulate VEGF activity in culture and in vivo. For example, VEGF loaded hydrogels containing heparin binding peptide amphiphiles potentiated VEGF signaling in culture and in vivo, and VEGF loaded hydrogels containing fibronectin-mimicking peptides increased VEGF-dependent EC function in vitro and increased neovascularization in vivo. Fibronectin and heparin, however, can promiscuously bind multiple growth factors, and are thus limited in their ability to regulate VEGF with specificity.
Based on the foregoing, there is a need in the art for a synthetic biomaterial that can regulate growth factors, and regulate VEGF selectively, such to allow improved wound healing. It would be particularly advantageous if the biomaterial could remove VEGF from solution, such as autologous blood products, allowing for intra-operative processing of blood products before the products are used in clinical procedures.